1) In the last several years a number of lymphokines have been described which play important roles in growth and/or differentiation of B- and T-lymphocytes. Studies from this laboratory have identified an activity in supernatants from macrophage cell lines which is required by early plasmacytomas for growth and viability in vitro. As part of our current interest in control of cell growth, a major effort is being made to characterize this factor and determine its role in vivo. Ultimately, we plan to extend these studies to the receptor for this factor in order to assess the potential biological role of this factor-receptor system in normal cell growth and/or possibly plasmacytomagenesis. 2) A second major interest in the area of growth and differentiation is directed toward an attempt to isolate and characterize genes (and their protein products) involved in ontological differentiation of lymphoid cells. To approach this question, we have developed new or selected existing cell lines which can be induced to differentiate. The strategy of these experiments is to prepare subtractive cDNA libraries using the parental line and the differentiated derivatives. The resulting clones will then be analyzed with the eventual aim of transfecting isolated genes back into the parental cell type of attempt to reproduce the differentiated phenotype in the absence of inducing agent. 3) Mutational processes operating during gene evolution may range from relatively simple, such as point mutation, to considerably more complex, such as recombination, gene conversion, expansion and contraction. Most evolutionary studies in higher organisms have involved comparisons of similar protein or gene sequences from two or more species which are generally widely separated in evolutionary time. We have attempted to assess the role of such processes in a more dynamic context by examining gene structures among different wild mice species. We have therefore initiated experiments to examine single copy genes, pauci-gene families and multi-gene families among our wild mice colony representing the evolutionary spectrum of this species.